DESCRIPTION: The proposed study is part of a broad interest by the applicant in the genetic mechanisms that establish distinct tissues and organs during embryogenesis, including both the initial instructions that define an organ and the subsequent cell-cell signaling, changes in gene expression, and cellular movements that build the differentiated organ and maintain its identity. Study of salivary gland development in Drosophila embryos has led to a model for the initial determination of cells in the salivary primordium. Salivary gene expression is activated by the homeotic gene Sex combs reduced, and the salivary gland and salivary duct primordia are distinguished from each other by the opposing activities of the EGF receptor signaling pathway and the transcription factor fork head. Nevertheless, neither the effectors nor the targets of EGFR signaling have been defined. Shortly after their determination, salivary glands begin to form by an orderly invagination that begins at the posterior dorsal edge of the placode and continues to the anterior and then ventral parts of the placode. The ducts form by a continuation of the placode invagination to produce the Y-shaped ducts that are much smaller in diameter than the glands. Although this morphogenesis is highly ordered, its genetic control is just beginning to be investigated. There are five Specific Aims for these experiments: 1) identify the spitz-dependent repressors that prevent fkh expression in the pre-duct cells. 2) define the roles of senseless and daughterless. Do they antagonize the effects of the EGFR pathway; 3) determine whether huckebein and wingless interact to initiate and organize salivary invagination; 4) test whether the Tec29 tyrosine kinase regulates cell division in the salivary placode to facilitate salivary morphogenesis; and 5) use a sensitized genetic screen to identify genes required for salivary duct development.